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Evaluating Long-Term Effectiveness of Cystic Fibrosis Modulator Therapies after Rapid Adoption: A Dual-Approach Study.
Get PDFRATIONALE: Modulator therapies like ivacaftor have revolutionized clinical management of cystic fibrosis, showing marked short-term benefits in trials but heterogeneous findings in long-term observational studies. Since newer modulators have become the standard of care for the majority living with cystic fibrosis in the United States, characterizing long-term effectiveness with real-world data is increasingly difficult because of the lack of contemporary comparator groups for performing between-subjects analyses.
OBJECTIVES: To determine the extent to which ivacaftor preserves long-term lung function and compare the results of within- and between-subjects analyses for evaluating its real-world effectiveness.
METHODS: This retrospective cohort study used data from the U.S. Cystic Fibrosis Foundation Patient Registry (2003-2016). We used two approaches to evaluate ivacaftor effectiveness on percent predicted forced expiratory volume in 1 second (ppFEV1): 1) within-subject comparisons of ppFEV1 before and after ivacaftor initiation; and 2) comparisons between ivacaftor-treated and untreated individuals with similar disease pathology. We modeled data from 560 ivacaftor-treated individuals with the G551D variant. For between-subjects comparisons, we used propensity scores to match the treated group with 2,800 untreated F508del homozygous individuals. Modulator initiation bias was assessed and accounted for in each model.
RESULTS: Our results showed an initial average improvement in ppFEV1 in ivacaftor-treated children and adults (ranging from 4.54% to 6.53% predicted based on within-subject comparison of before vs. after ivacaftor initiation). There was a slower decline in adults, compared with children. These ivacaftor-treated cohorts experienced less decline relative to their F508del homozygous counterparts (between-group differences in treated vs. control ranged from 0.36% to 0.64% predicted). Both the within- and between-subjects comparisons demonstrated similar degrees of ivacaftor effectiveness. However, small differences between the two approaches were observed in younger individuals.
CONCLUSIONS: Ivacaftor was associated with improved ppFEV1 across all age groups, with the magnitude of improvement roughly 50% of that observed in clinical trials. The results support the need to account for modulator initiation bias and the use of within-subject analysis in future CFTR (cystic fibrosis transmembrane conductance regulator) modulator effectiveness studies, but caution is advised in younger individuals because of developmental changes that may affect pre- and post-treatment comparability
Associations of chronic obstructive pulmonary disease with life satisfaction and self-rated health: quantifying the subjective burden in a population-based study.
Get PDFINTRODUCTION: Subjective health and wellbeing measures such as self-rated health and life satisfaction are widely used in population health research and surveillance, yet their ability to reflect the lived burden of chronic disease has rarely been tested directly. This cross-sectional study examined whether life satisfaction and self-rated health differ between individuals with and without chronic obstructive pulmonary disease (COPD).
METHODS: We used pooled data from the 2018, 2019, 2021, and 2022 waves of the Scottish Health Survey, comprising 18,563 adults aged 16 years and over. COPD status was determined through self-report of a doctor diagnosis. Life satisfaction was categorised as low (0–7), moderate (8), or high (9–10), and self-rated health was grouped as very good/good, fair, or bad/very bad. Ordinal logistic regression was used to estimate unadjusted associations and generalised ordered logistic regression was applied for adjusted models, controlling for age, sex, smoking, ethnicity, education, mental health, area deprivation, and urban/rural residence.
RESULTS: Individuals with COPD had significantly poorer subjective wellbeing. In unadjusted models, individuals with COPD had 60% lower odds of reporting higher life satisfaction (OR = 0.40; 95% CI 0.35–0.46) and nearly nine times the odds of reporting worse self-rated health (OR = 8.70; 95% CI 7.64–9.92) compared to those without COPD. After adjustment, these associations remained strong: COPD was associated with 49% lower odds of higher life satisfaction (OR = 0.51; 95% CI 0.44–0.59) and over fourfold higher odds of poor self-rated health (OR = 4.24; 95% CI 3.68–4.89).
CONCLUSIONS: Self-rated health and life satisfaction clearly distinguish individuals with COPD from those without, supporting their construct validity as indicators of chronic disease burden in population-based surveys. These brief measures may offer valuable tools for public health monitoring and evaluation of health inequalities
UK cancer vaccine advance – Recognising and realising opportunities
Get PDFVaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology
Evidence required to evaluate the use of bacteriologically confirmed asymptomatic tuberculosis disease as a primary endpoint in prevention of tuberculosis disease vaccine licensure trials.
No full textCurrent licensure trials of new vaccines to prevent tuberculosis disease use bacteriologically confirmed symptomatic tuberculosis disease as the primary endpoint. Globally, the incidence of symptomatic tuberculosis disease is low, making licensure trials large, long, and expensive. New data suggest that bacteriologically confirmed asymptomatic tuberculosis disease might occur more frequently than symptomatic tuberculosis disease. Therefore, if vaccines have efficacy against asymptomatic disease, tuberculosis vaccine licensure trials could include it in the primary endpoint, potentially leading to smaller or shorter trials. We describe the potential benefits and risks of this inclusion in the primary endpoint of tuberculosis vaccine licensure trials. We also simulate licensure trial endpoint accrual and summarise feedback from anonymous regulators and policy makers on the knowledge needed to consider this proposal and research studies needed to fill these evidence gaps. If bacteriologically confirmed asymptomatic tuberculosis disease could be included in the primary endpoint of tuberculosis disease licensure trials, it could lead to cheaper and more rapid tuberculosis vaccine development
Adaptation and Validation of Brief Tablet‐Based Cognitive Assessment Tool in Uganda
Get PDFAbstract
Background
Sub‐Saharan Africa (SSA) faces accelerated growth of older adults, older people living with HIV (PLWH), and Alzheimer's Disease (AD). However, there is a shortage of human resources and contextually relevant diagnostic tools to assess cognitive impairment (CI) in the region. The tablet‐based Cognitive Assessment Tool (TabCAT) is a brief digital battery with automated scoring which can be administered by non‐specialists across diverse cultures, languages, and education levels. We assessed its performance in the Uganda Aging Cohort Study (UACS), a prospective cohort study of older PLWH and age‐ and sex‐similar HIV‐uninfected adults in Uganda.
Method
TabCAT tests were translated and culturally adapted through expert review and focus groups. We compared TabCAT scores against performance on a reference‐standard cognitive testing battery previously validated and employed in Uganda. Z‐scores on all tests were derived using a regression‐based normative approach to adjust for age, sex, and education. CI was defined using Jak/Bondi criteria. TabCAT test performances were examined for floor and ceiling effects, with concurrent and divergent validity determined via Spearman rank correlations. Receiver Operating Characteristic (ROC) curves were fit to assess TabCAT composite score discriminative ability for CI in the sample and by HIV serostatus.
Result
TabCAT measures were regarded to have acceptable face and content validity by local experts and focus groups. Participants (
n
= 563, mean age 60±6.5, 50% female, 51% < primary school, 49% PLWH) completed the reference‐standard and TabCAT battery. For TabCAT tests, there were no notable floor or ceiling effects. Correlations between TabCAT and reference‐standard tests were strongest in overlapping cognitive domains (memory, executive function) and weakest in unrelated motor domains (Figure 1). The TabCAT composite score identified CI with good to excellent performance (c‐statistic 0.79; 95% CI 0.74‐0.83), with similar performance in PLWH (Figure 2).
Conclusion
TabCAT tests demonstrate content, concurrent, and criterion validity for identifying CI in a SSA population and in PLWH. Despite variability in concurrent validity on some tests, TabCAT is a promising brief assessment tool to identify CI with generalizability across diverse cultures, languages, education levels, and HIV serostatus. Future studies will examine TabCAT validity for assessing and diagnosing AD and related dementias in Uganda and other resource‐limited settings
A case study of partnership in practice: challenges and insights in the development of an academic-community coalition "The Migrant Health Community Research Network".
Get PDFBACKGROUND: Participatory research (PR) approaches are increasingly prioritised globally, particularly in the UK, where many funders have emphasised meaningful collaboration with those with lived experience to improve health research relevance, translation and impact. Despite this, marginalised groups, such as migrants, remain underrepresented in research, perpetuating health inequities. Migrants, who comprise 16% of the UK population, face systemic barriers to engagement, including distrust, hierarchical academic structures, and lack of inclusivity. PR approaches offer a collaborative framework for empowering migrant voices, balancing research and action, and fostering trust to address these disparities. This case study describes the development of the Migrant Health Community Research Network (MHCRN), a collaboration between migrant community groups, individuals, academics and health professionals from the Migrant Health Research Group, City St Georges University of London (MHRG). Aim MHRG sought to develop a sustainable model for engaging migrants in health research through a co-created network addressing power imbalances and ensuring inclusivity.
METHODS: MHRG adopted PR principles, reflecting on the groups collective experience of prior engagement practices and systematically reviewing best practices. A five-phase approach was used: (1) defining agenda and aspirations through group reflection; (2) identifying concerns and challenges through internal reflection and community consultation; (3) conducting community exploratory workshops with co-facilitation; (4) establishing initial network structure based on collectively agreed principles; (5) co-developing a lived experience advisory panel.
FINDINGS: The process has resulted in the following outputs: the “Migrant Health Community Research Network” (MHCRN) with guiding principles (equity, diversity, respect, decolonisation, empowerment, community), a network steering group (LEAP, Lived Experience Advisory Panel), community-based collaborations embedding migrant voices at all research stages, capacity building through training and peer researcher roles, and award-winning projects. Key challenges identified include structural inequalities, funding limitations, and institutional barriers. Opportunities emerged around trust-building, shared leadership, and sustainable relationship development.
CONCLUSIONS: While the MHCRN represents an important step in embedding meaningful collaboration, challenges persist. This initiative highlights the need for systemic change in academia to support equitable partnerships and inform similar innovative initiatives. By prioritizing non-tokenistic engagement and co-production, the MHCRN sets a foundation for sustained, impactful collaboration to address health inequities and inform policy and practice.
PLAIN ENGLISH SUMMARY: Many health research projects fail to involve people they aim to help, especially marginalised groups such as migrants. This often results in research that is neither relevant nor useful. We recognised that the way we have worked with people with lived experience of migration could be improved. Our aim was to create a way to work together long-term so that migrant voices are heard and acted on from the development of research ideas all the way to the delivery and sharing of findings. We decided after talking to many researchers, migrants, community organisations and health care professionals that a migrant health research network that brought together all these voices through relationship building and creative ways of working and sharing ideas would be a good way to do this. We established the Migrant Health Community Research Network (MHCRN) which brings together people living in the United Kingdom with lived experience of migration from all over the world, healthcare professionals working in the National Health Service (NHS) and researchers from City St George’s University of London to improve migrant health. Our network was built step-by-step, starting with open conversations with migrants, healthcare professionals and researchers about challenges they had experienced in involving migrant communities in research and how these could be overcome. We then ran a workshop to shape our vision and agreed on shared principles. The network aims to be long-term, inclusive, and led by those with lived migration experience. Although there are ongoing challenges, this process has taught us valuable lessons about working together in a meaningful way
Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case-control study.
Get PDFSevere pediatric malaria remains a pressing global health issue. Laboratory parameters may provide early risk and severity stratification for better disease management, beyond current clinical severity scores. This study aimed to identify host biomarkers of immune and endothelial activation and parasite biomass in children with severe malaria (SM) compared to uncomplicated malaria (UM). We conducted a case-control study in a rural hospital in southern Mozambique from 2014 to 2016, recruiting patients under 10 years old with Plasmodium falciparum SM as cases, and patients with UM matched by age, sex, and parasitemia as controls. We compared plasma levels of biomarkers associated with total parasite mass (HRP-2), biomarkers of host response to infection (Angpt-1, Angpt-2, sTie-2, BDNF, CysC, sFlt-1, IL-6, IL-8, IP-10, sTNFR-1 and sTREM-1). All biomarker levels except Angpt-1, BDNF and CysC were significantly higher in children with SM. HRP-2 levels significantly differed between cases and controls, strongly correlating with Angpt-2, sTie-2, sFlt-1, TNRF, and sTREM-1, both in SM and UM. In conclusion, host biomarkers indicative of immune and endothelial activation were associated with malaria severity and HRP-2, even after controlling for matching variables, potentially offering targets for risk-stratification and adjuvant therapy
Indicators for effective glaucoma care coverage in adults: protocol for a scoping review.
Get PDFINTRODUCTION: Glaucoma is the leading cause of irreversible blindness worldwide and the number of people with glaucoma is expected to increase to more than 112 million by the year 2040, making it a disease of public health interest. However, there is no consensus on public health indicators to monitor glaucoma care coverage. This scoping review aims to summarise published indicators for monitoring effective glaucoma care coverage globally, focusing on care needs, use of care services and outcomes achieved. METHODS AND ANALYSIS: We will include studies that report the development and use of public health indicators for effective glaucoma care coverage in patients aged 18 years and older. Studies published from 1 January 2000, in all languages, will be included, provided they can be accurately and easily translated into English using Google Translate. Searches will be conducted by an information specialist on MEDLINE, Embase, Global Health and CENTRAL in the Cochrane Library. Two reviewers working independently will screen the search results, select studies for inclusion and extract data; any disagreements will be discussed with or resolved by a third reviewer. Data will be presented in tabular form, followed by a narrative synthesis based on the review objectives. ETHICS AND DISSEMINATION: Ethical approval is not required as the review will use published data. Results will be published in a peer-reviewed journal, and summarised results will be available and contribute to the development of standardised glaucoma care indicators. REGISTRATION: OSF registration on 19 May 2025: https://osf.io/zsyw9/
A Framework for Incorporating a Disability Lens in Women’s Reproductive Health Research and Practice for Healthy Life Trajectories
Get PDFWe present a framework developed through disability and reproductive health expert consensus to guide the adaptation of interventions for healthy life trajectories to meet the needs of women with disabilities. We conducted a scoping review of support available for women with disabilities, in-depth interviews with experts from the disability and reproductive health sectors, and a group consensus-building process for framework development with expert participants from the disability and reproductive health sectors. Findings identified challenges to disability-inclusive care in reproductive health services. Recommendations include tailored actions to specific stakeholders within their scope of practice to work toward disability-inclusive health care for persons with disabilities
Examining the effect of universal testing and treatment strategies for HIV prevention in Zambia and South Africa: generalizing the results of the HPTN 071 (PopART) trial.
Get PDFINTRODUCTION: HIV Prevention Trials Network (HPTN) 071 (PopART) was a cluster-randomized trial to evaluate universal testing and treatment (UTT) strategies for HIV prevention. HPTN071 compared three arms: (A) combination prevention with UTT; (B) combination prevention with universal testing and antiretroviral therapy initiation according to local guidelines; and (C) standard of care (SOC). Interventions were implemented in entire randomized communities, with impacts on HIV incidence measured in "population cohorts," that is the HPTN071 sample. Unexpectedly, a significantly lower incidence was not observed in arm A relative to SOC. Importantly, rates of participation in the HPTN071 sample differed among population subgroups, for example men were underrepresented.
METHODS: To correct for underrepresented subgroups, PopART intervention effects are estimated in a population of interest, adults aged 18-44 in trial provinces, characterized with two nationally representative HIV-focused surveys. The HPTN071 sample is weighted to match the population of interest by demographics and HIV risk factors. Risk of HIV acquisition is compared across arms, both in the trial population (unweighted) and the population of interest (weighted). Both (1) the risk of HIV acquisition between 1 and 3 years and (2) the risk of HIV acquisition by 3 years are compared.
RESULTS: In the trial population, estimated risk in arm A is, counterintuitively, slightly higher than SOC (Year 1-3 Risk Difference [RD]: 0.10%; 95% CI: -1.15%, 1.25%). After weighting, risk in arm A is lower than SOC in the population of interest (RD: -0.34%; 95% CI: -2.04%, 0.96%). Weighting also strengthened the estimated effect in arm B relative to SOC (unweighted RD: -0.66%, 95% CI: -1.88%, 0.46%; weighted RD: -1.18%, 95% CI: -2.85%, 0.15%). Weighted year 3 risk difference estimates indicated even stronger possible intervention effects: A versus SOC -0.83% (95% CI: -2.94%, 0.99%), B versus SOC -1.86% (95% CI: -3.80%, -0.09%).
CONCLUSIONS: PopART interventions are estimated to be more protective in the population of interest than observed in the HPTN071 sample. These results partially explain the unexpected finding in arm A, providing further support for UTT strategies for HIV prevention. This analysis also highlights the importance of considering heterogeneous treatment effects among population subgroups when measuring the overall efficacy of HIV interventions